Yu Anping, Fu Feng, Li Xiongying, Wu Mengxin, Yu Meijian, Zhang Wenxiong
Department of Oncology, Fengcheng People's Hospital, Yichun, China.
Department of Oncology, The Affiliated Fengcheng Hospital of Yichun University, Yichun, China.
Front Oncol. 2024 Feb 22;14:1351359. doi: 10.3389/fonc.2024.1351359. eCollection 2024.
In recent years, we have observed the pivotal role of immunotherapy in improving survival for patients with non-small cell lung cancer (NSCLC). However, the effectiveness of immunotherapy in the perioperative (neoadjuvant + adjuvant) treatment of resectable NSCLC remains uncertain. We conducted a comprehensive analysis of its antitumor efficacy and adverse effects (AEs) by pooling data from the KEYNOTE-671, NADIM II, and AEGEAN clinical trials.
For eligible studies, we searched seven databases. The randomized controlled trials (RCTs) pertaining to the comparative analysis of combination neoadjuvant platinum-based chemotherapy plus perioperative immunotherapy (PIO) versus perioperative placebo (PP) were included. Primary endpoints were overall survival (OS) and event-free survival (EFS). Secondary endpoints encompassed drug responses, AEs, and surgical outcomes.
Three RCTs (KEYNOTE-671, NADIM II, and AEGEAN) were included in the final analysis. PIO group (neoadjuvant platinum-based chemotherapy plus perioperative immunotherapy) exhibited superior efficacy in OS (hazard ratio [HR]: 0.63 [0.49-0.81]), EFS (HR: 0.61 [0.52, 0.72]), objective response rate (risk ratio [RR]: 2.21 [1.91, 2.54]), pathological complete response (RR: 4.36 [3.04, 6.25]), major pathological response (RR: 2.79 [2.25, 3.46]), R0 resection rate (RR: 1.13 [1.00, 1.26]) and rate of adjuvant treatment (RR: 1.08 [1.01, 1.15]) compared with PP group (neoadjuvant platinum-based chemotherapy plus perioperative placebo). In the subgroup analysis, EFS tended to favor the PIO group in almost all subgroups. BMI (>25), T stage (IV), N stage (N1-N2) and pathological response (with pathological complete response) were favorable factors in the PIO group. In the safety assessment, the PIO group exhibited higher rates of serious AEs (28.96% vs. 23.51%) and AEs leading to treatment discontinuation (12.84% vs. 5.81%). Meanwhile, although total adverse events, grade 3-5 adverse events, and fatal adverse events tended to favor the PP group, the differences were not statistically significant.
PIO appears to be superior to PP for resectable stage II-III NSCLC, demonstrating enhanced survival and pathological responses. However, its elevated adverse event (AE) rate warrants careful consideration.
https://www.crd.york.ac.uk/PROSPERO/#recordDetails, identifier CRD42023487475.
近年来，我们观察到免疫疗法在改善非小细胞肺癌（NSCLC）患者生存率方面发挥着关键作用。然而，免疫疗法在可切除NSCLC围手术期（新辅助+辅助）治疗中的有效性仍不确定。我们通过汇总KEYNOTE-671、NADIM II和AEGEAN临床试验的数据，对其抗肿瘤疗效和不良反应（AE）进行了综合分析。
对于符合条件的研究，我们检索了七个数据库。纳入了关于新辅助铂类化疗联合围手术期免疫疗法（PIO）与围手术期安慰剂（PP）对比分析的随机对照试验（RCT）。主要终点为总生存期（OS）和无事件生存期（EFS）。次要终点包括药物反应、AE和手术结果。
最终分析纳入了三项RCT（KEYNOTE-671、NADIM II和AEGEAN）。与PP组（新辅助铂类化疗联合围手术期安慰剂）相比，PIO组（新辅助铂类化疗联合围手术期免疫疗法）在OS（风险比[HR]：0.63[0.49-0.81]）、EFS（HR：0.61[0.52,0.72]）、客观缓解率（风险比[RR]：2.21[1.91,2.54]）、病理完全缓解（RR：4.36[3.04,6.25]）、主要病理缓解（RR：2.79[2.25,3.46]）、R0切除率（RR：1.13[1.00,1.26]）和辅助治疗率（RR：1.08[1.01,1.15]）方面表现出更高的疗效。在亚组分析中，几乎所有亚组的EFS都倾向于PIO组。BMI（>25）、T分期（IV期）、N分期（N1-N2）和病理反应（有病理完全缓解）是PIO组的有利因素。在安全性评估中，PIO组严重AE发生率（28.96%对23.51%）和导致治疗中断的AE发生率（12.84%对5.81%）更高。同时，尽管总不良事件、3-5级不良事件和致命不良事件倾向于PP组，但差异无统计学意义。
对于可切除的II-III期NSCLC，PIO似乎优于PP，显示出更高的生存率和病理反应。然而，其较高的不良事件（AE）发生率值得仔细考虑。
https://www.crd.york.ac.uk/PROSPERO/#recordDetails，标识符CRD42023487475。
